10-(Cyclopropylcarbonyl)-3'-Dephenyl-3'-(2-methyl-2-propenyl)docetaxel

ID: ALA126916

PubChem CID: 9897471

Max Phase: Preclinical

Molecular Formula: C45H59NO15

Molecular Weight: 853.96

Molecule Type: Small molecule

Names and Identifiers

Synonyms: SB-T-1214 | SB-T-1214|CHEMBL126916|SCHEMBL17971155|[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-Acetyloxy-12-(cyclopropanecarbonyloxy)-1,9-dihydroxy-15-[(2R,3S)-2-hydroxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate

Canonical SMILES:  CC(=O)O[C@@]12CO[C@@H]1C[C@H](O)[C@@]1(C)C(=O)[C@H](OC(=O)C3CC3)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@H](C=C(C)C)NC(=O)OC(C)(C)C)C[C@@](O)([C@@H](OC(=O)c4ccccc4)[C@H]21)C3(C)C

Standard InChI:  InChI=1S/C45H59NO15/c1-22(2)18-27(46-40(54)61-41(5,6)7)32(49)39(53)57-28-20-45(55)36(59-38(52)25-14-12-11-13-15-25)34-43(10,29(48)19-30-44(34,21-56-30)60-24(4)47)35(50)33(58-37(51)26-16-17-26)31(23(28)3)42(45,8)9/h11-15,18,26-30,32-34,36,48-49,55H,16-17,19-21H2,1-10H3,(H,46,54)/t27-,28-,29-,30+,32+,33+,34-,36-,43+,44-,45+/m0/s1

Standard InChI Key:  WPPTYUSIXLFOKZ-BYOOWSCBSA-N

Molfile:  

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M  END

Alternative Forms

1. Parent:

   

   ALA126916

   CID 9897471

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 853.96

Molecular Weight (Monoisotopic): 853.3885

AlogP: 3.81

#Rotatable Bonds: 10

Polar Surface Area: 230.52

Molecular Species: NEUTRAL

HBA: 15

HBD: 4

#RO5 Violations: 2

HBA (Lipinski): 16

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 11.81

CX Basic pKa: ┄

CX LogP: 3.77

CX LogD: 3.77

Aromatic Rings: 1

Heavy Atoms: 61

QED Weighted: 0.15

Np Likeness Score: 1.96

References

1. Ojima I, Slater JC, Michaud E, Kuduk SD, Bounaud PY, Vrignaud P, Bissery MC, Veith JM, Pera P, Bernacki RJ..  (1996)  Syntheses and structure-activity relationships of the second-generation antitumor taxoids: exceptional activity against drug-resistant cancer cells.,  39  (20): [PMID:8831755] [10.1021/jm9604080]

2. Kuznetsova L, Chen J, Sun L, Wu X, Pepe A, Veith JM, Pera P, Bernacki RJ, Ojima I..  (2006)  Syntheses and evaluation of novel fatty acid-second-generation taxoid conjugates as promising anticancer agents.,  16  (4): [PMID:16298526] [10.1016/j.bmcl.2005.10.089]

3. Ojima I, Chen J, Sun L, Borella CP, Wang T, Miller ML, Lin S, Geng X, Kuznetsova L, Qu C, Gallager D, Zhao X, Zanardi I, Xia S, Horwitz SB, Mallen-St Clair J, Guerriero JL, Bar-Sagi D, Veith JM, Pera P, Bernacki RJ..  (2008)  Design, synthesis, and biological evaluation of new-generation taxoids.,  51  (11): [PMID:18465846] [10.1021/jm800086e]

4. Ojima I, Das M..  (2009)  Recent advances in the chemistry and biology of new generation taxoids.,  72  (3): [PMID:19239240] [10.1021/np8006556]

5. Matesanz R, Trigili C, Rodríguez-Salarichs J, Zanardi I, Pera B, Nogales A, Fang WS, Jímenez-Barbero J, Canales A, Barasoain I, Ojima I, Díaz JF..  (2014)  Taxanes with high potency inducing tubulin assembly overcome tumoural cell resistances.,  22  (18): [PMID:25047938] [10.1016/j.bmc.2014.05.048]

6. Seitz JD, Vineberg JG, Herlihy E, Park B, Melief E, Ojima I..  (2015)  Design, synthesis and biological evaluation of a highly-potent and cancer cell selective folate-taxoid conjugate.,  23  (9): [PMID:25819334] [10.1016/j.bmc.2015.02.057]

7. Ojima I, Wang X, Jing Y, Wang C..  (2018)  Quest for Efficacious Next-Generation Taxoid Anticancer Agents and Their Tumor-Targeted Delivery.,  81  (3): [PMID:29468872] [10.1021/acs.jnatprod.7b01012]

8. Yang CH, Wang C, Ojima I, Horwitz SB..  (2018)  Taxol Analogues Exhibit Differential Effects on Photoaffinity Labeling of β-Tubulin and the Multidrug Resistance Associated P-Glycoprotein.,  81  (3): [PMID:29517223] [10.1021/acs.jnatprod.7b01047]

Source

Source(1):

• Scientific Literature